Connecting the Microbiome and Antibiotics to Obesity

Tracing a Path From Campylobacter to the Microbiome

Eric J. Topol, MD: Hello. I'm Eric Topol, editor-in-chief of Medscape, and I am pleased to have Dr Martin Blaser join me for this One-on-One interview. Dr Blaser runs the Human Microbiome Center at New York University, and has been a leader in infectious diseases for decades. It's great to have a chance to talk to you about the hottest area of medicine today: the microbiome.

You got into this area decades ago. Did you ever think when you were working on Helicobacter that it was going to blossom into such a central aspect of the future of medicine?

Martin J. Blaser, MD: No. That is the great thing about a career in science: You don't know exactly where it's going to lead you. When I was working on diseases of the stomach, I had no idea that it would lead me into allergy, obesity, and diabetes.

Dr Topol: You were more of a traditional infectious disease specialist when you started.

Dr Blaser: Yes; clinically, I was a specialist in infectious disease, and my research was about pathogens. I started with Campylobacter, an organism that causes diarrhea, and then a new Campylobacter was discovered in the stomach. It was also called Campylobacter, but ultimately they changed the name to Helicobacter pylori. I'm still following the thread that began in 1977, when I saw a patient with Campylobacterbacteremia.

Dr Topol: Did you have the same experience as Barry Marshall—that no one believed any of this stuff?

Dr Blaser: Some of that has been embellished over the years. I was at the first international conference when Barry presented his work, and it was clear that he had found a new organism in the stomach. Within months, there were papers in The Lancet, replicating his findings and finding the association, but over the years Barry and the others showed that eliminating Helicobacter changed the natural history of ulcer disease. That was obviously a big finding. They won the Nobel Prize for that, and it was an important observation.

Then, we and others showed that Helicobacter was important in stomach cancer, which is the second leading cause of cancer death in the world.

Dr Topol: As you pointed out in our program, understanding the root cause of a pathogen can markedly change the incidence.

Dr Blaser: Actually, the incidence changed even before Helicobacter was discovered.

Dr Topol: Is that right?

Dr Blaser: It started declining in the 1930s, probably because of clean water and smaller families. We are not sure of all the factors. In 1900, gastric cancer was the number one cause of cancer death in the United States. Now it has decreased 10-fold.

Dr Topol: Has the understanding accelerated the reduction?

Dr Blaser: That's hard to know, because the understanding is relatively recent and gastric cancer is a disease that takes decades to develop. It probably develops over 60 years, on average.

The Microbiome's Influence on Disease and Health

Dr Topol: Let's fast-forward from when you got your start with Campylobacter research to the point where the microbiome seems to be responsible for everything. You have written this phenomenal book, Missing Microbes (Picador, 2015) which really delves into this topic broadly. What things should we acknowledge as real? What things are too much of a reach? Where are we with the microbiome in terms of influencing disease and health today?

Dr Blaser: I'm working in a particular area of the microbiome. It's an area that I think has importance.

The basic idea is that the microbiome is ancient. The organisms that we carry are not random; they have been selected over eons of evolution. They are important for our physiology, and there is a lot of evidence for that. My big point is that they are changing. As a result of the change, there are health consequences.

One of the good health consequences is that as Helicobacter is disappearing, there is less stomach cancer. That's good news, but as Helicobacter is disappearing, there is more esophageal disease and asthma. Both of these have been linked to the lack of Helicobacter.

I believe that there is a general paradigm that we are losing important organisms early in life, and that is fueling some of the diseases that are epidemic today. We have been studying this in the lab.

Dr Topol: You have noted many factors, such as the big rise in C-sections, that changes flora from birth, and the use of antibiotics in a promiscuous way. What other factors have been contributing to this? What practices are changing the landscape of disease?

Dr Blaser: Those are the two biggest factors, as far as I can tell at this time, but there are a lot of things that we just don't understand. One of my hypotheses, which is really alarming—and it's why I wrote the book—is that the effects are cumulative over time and cumulative across generations.

If they are cumulative, that means that C-sections plus antibiotics are important. The second antibiotic is important, not only the first one, and maybe all the washing and the antiseptics and even the clean water.

Clean water is an amazing blessing. We don't have such diseases as typhoid fever or cholera, but by eliminating pathogens, we have also eliminated the commensals that travel between us. There is a hidden cost there.

Linking Livestock Growth to Human Waistline Growth

Dr Topol: Do you think that obesity in epidemic proportions is anchored to the microbiome changes?

Dr Blaser: I do, and that is a central area of the work that we are doing. It is based on an observation that goes back 70 years. Farmers found that they could increase the growth of their livestock by giving them low doses of antibiotics. They found that the earlier in life they gave the antibiotics, the more profound the effect—and that is what we are doing to our kids.

Dr Topol: Beyond the antibiotic use, there have been changes in diet. For example, dietary guidelines—the low-fat diets with high carbohydrates, or the diets with high red meat ingestion—do these dietary changes have a material effect?

Dr Blaser: The most important dietary change is the move from breast milk to formula. That is the most important. There is a lot of evidence that obesity is beginning in childhood. It's beginning very early. The seeds are there, and that is fueling the growth, even before kids have a chance to become couch potatoes. It's before there are big changes in diet.

We've done studies in mice in which we can show that giving mice antibiotics early in life makes them fat. Putting mice on a high-fat diet makes them fat, and putting them on both together makes them very fat, suggesting the idea of additive risk.

Dr Topol: What about the notion that changes in the diet—for example, introducing artificial sweeteners—cause changes in the microbiome and the associated adverse effects? So many of these things are coming out now. Peanut allergies—you name it, there is a connection with the microbiome. Are we buying into that, or will it take a lot more proof to link all this together?

Dr Blaser: The microbiome is a big place, just like human genetics is a big place.

Dr Topol: Maybe even bigger.

Dr Blaser: All important science needs confirmation. I am focusing on the early events. When someone has had obesity for 50 years, it's hard to tease out.

Peanut allergy is a good example. It used to be quite uncommon and now it's quite common. What has happened? It begins in childhood, as certain allergies and asthma begin in childhood. That is where we are focusing our work: on early development.

Dr Topol: The increase in allergies and asthma—how do we link those together? Is it the antibiotics and the C-sections? Is that it?

Dr Blaser: In a word, yes. The reason is that the early-life microbiota helps choreograph development. It choreographs metabolic development and immune development. The microbiota teaches the developing immune system what is self and what is not self. Of course we are changing it, I believe, in a substantial way.

Send in Your Stool Sample

Dr Topol: A couple other things are going on in this field that I would love to get your comments on. One is about using drugs and preparations to change the microbiome, potentially restoring it to the way it used to be before we screwed it up. There are new companies cropping up. This is beyond probiotics. What are your thoughts about whether we will be able to engineer, in a salutary way, the microbiome?

Dr Blaser: We are at the beginning of a big scientific front here. I believe that we are going to have great probiotics in the future that will be scientifically developed—not the stuff that is available in hundreds of different compounds and pharmacies, health food stores, and grocery stores. The shelves are loaded with compounds called "probiotics." What I can say is that they are generally safe and almost completely untested.

Dr Topol: The other thing that is starting to be the rage is people analyzing their own gut microbiomes through a stool sample, through such companies as uBiome and American Gut. What are your thoughts about that?

Dr Blaser: Right now, the information is unlikely to be useful to anybody. I sent my sample to American Gut. I haven't got around to looking at it. One day that information or some fraction of that information might be useful, but we don't know which fraction it's going to be.

Dr Topol: Will we come to a new way of using the microbiome to predict and prevent illness in the future?

Dr Blaser: When doctors of the future examine a baby, they are going to be very interested in analyzing that baby's diaper and trying to figure out which microbes are present and which ones might have to be replaced, Are the global microbes that every baby needs present? Are some missing that might be needed by that particular baby?

Dr Topol: What were your thoughts about McDonalds getting rid of antibiotic-fed chickens? Is that a step in the right direction?

Dr Blaser: Absolutely. Our microbiome is being influenced in so many different ways because farmers are using so many antibiotics that they are getting into meats and milk to some degree. Antibiotics are in the water supply of people who live downstream of the effluent of these industrial farms.

In China it's just amazing, because they are using 10 times as much antibiotic on the farms as we are. In some cities, you can measure the antibiotic concentrations in the water. People in China are growing.

Dr Topol: The insights that you provided throughout your career and through your center at New York University have been phenomenal, so it's great to visit with you and hear your thoughts. You certainly qualify as one of the most interesting people in medicine. I hope that everybody in our Medscape audience will learn more about the microbiome through your efforts and read your book.

Thanks so much for joining us, and thank all of you for joining this Medscape One-on-One interview.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.